Daunomycin, a known anthracycline antibiotic, is an antineoplastic agent of established clinical utility. Daunomycin consists of the aglycone, daunomycinone, and the amino sugar, daunosamine. A process for synthesizing daunosamine hydrochloride, as well as certain novel intermediates, is disclosed in U.S. Patent Application Ser. No. 128,299, filed concurrently herewith.
3',4'-epi-daunomycin consists of the aglycone, daunomycinone, and the amino sugar, ristosamine. 3',4'-epi-daunomycin has the formula: ##STR1##
3',4'-epi-daunomycin, like daunomycin, exhibits anti-tumor activity. See Arcamone et al., Synthesis of a Configurational Analog of Daunorubicin, Carbohydrate Research, Vol. 46, p. c3 (1976); Bargiotti et al., Synthesis of Derivatives of 3-Amino-2,3-dideoxy-L-hexoses Related to Daunosamine (3-Amino-2,3,6-Trideoxy-L-lyxo-hexose), Carbohydrate Research, Vol. 58, p. 353 (1977). Specifically, 3',4'-epi-daunomycin is effective against P-388 leukemia in mice. See U.S. Pat. No. 4,112,076 to Arcamone et al.
Since the amino sugar, ristosamine, provides an important part of 3',4'-epi-daunomycin, techniques for synthesizing ristosamine, and related compounds, are highly desirable as part of a technique for the total synthesis of 3',4'-epi-daunomycin.
Techniques for synthesizing L-ristosamine and related compounds are known. See, e.g., Lee et al., Confirmation by Synthesis of Ristosamine as 3-Amino-2,3,6-trideoxy-L-ribohexose, Journal of Medicinal Chemistry, Vol. 18, No. 7, p. 767 (1975); Sztaricskai et al., The Synthesis of N-Benzoylristosamine, Tetrahedron Letters, No. 13, p. 1111 (1975). Moreover, techniques for synthesizing D-ristosamine, an enantiomer of L-ristosamine, are also known. See, e.g., Pelyvas et al., A New Synthesis of D-ristosamine Derivatives, Carbohydrate Research, Vol. 53, p. c17 (1977); Baer et al., A Synthesis of 3-Amino-2,3,6-trideoxy-D-ribo-hexose (D-ristosamine) hydrochloride, Carbohydrate Research, Vol. 55, p. 253 (1977).
The techniques for synthesizing L-ristosamine disclosed by Lee et al., supra, and Sztaricskai et al., supra, both involve the potentially hazardous step of making an azide derivative with sodium azide. Moreover, in Sztaricskai et al. the reduction of the azide group to the amino group has a yield of only 36%.
The present invention provides a practical technique for synthesizing N-benzoyl-L-ristosamine. In addition, the present invention provides novel intermediates, and methods for their preparation, useful in synthesizing N-benzoyl-L-ristosamine.